Disease relevance of Vax1

• Mice carrying a targeted mutation of Vax1 show dysgenesis of the optic nerve, coloboma, defects in the basal telencephalon, and lobar holoprosencephaly [1].

High impact information on Vax1

• We provide genetic evidence that two closely related, ventrally expressed homeodomain proteins-Vax1 and Vax2-control this neuroepithelial segregation [2].
• This observation suggests that Vax1 may interfere negatively with the expression of Pax6 and Rx [1].
• The novel homeobox-containing gene Vax1, a member of the Emx/Not gene family, is specifically expressed in the developing basal forebrain and optic nerve [1].
• Vax1 therefore regulates the guidance properties of a set of anterior midline cells that orchestrate axon trajectories in the developing mammalian forebrain [3].
• This mapping assignment, together with the previously reported colocalization of Vax1 and Emx2 in mouse, indicates that the vax and the emx genes may be organized in clusters. vax2 has a remarkable expression domain confined to the ventral portion of the prospective neural retina in mouse, human, and Xenopus [4].

Biological context of Vax1

• The Vax1 gene is thus an interesting new tool to study the rostral ventral forebrain patterning, morphogenesis and evolution as well as the terminal differentiation of the forebrain in mouse and Xenopus [5].
• Vax1 chromosomal location is mapped at the distal end of the mouse chromosome 19, linked with that of Emx2 [5].
• RESULTS: We isolated two new mouse homeobox genes, Vax1 and Vax2, expressed in retina primordium [6].
• The SVZ of Vax1(-/-) brains is hyperplastic and mostly disorganized, and the RMS is missing, causing a failure of precursor cell migration to the OBs, which as a result are severely hypoplastic [7].

Anatomical context of Vax1

• Together, these observations suggest that Vax1 could have an early evolutionary origin and could participate in the specification and formation of the rostral and ventral forebrain in vertebrates [5].
• In mouse and Xenopus, Vax1 expression first occurs in the rostral neural plate, in the medial anterior neural ridge and adjacent ectoderm [5].
• Vax1 may contribute to differentiation of the neuroretina, pigmented epithelium and optic stalk, while Vax2 could function in the establishment of the dorso-ventral axis of the retina and the visual system [6].
• Compromised generation of GABAergic interneurons in the brains of Vax1-/- mice [8].
• We show that the absence of Vax1 causes a severe depletion of GABAergic neurons in the neocortex, ranging from 30% to 44%, depending on the cortical areas considered [8].

Other interactions of Vax1

• Vax1, a novel homeobox-containing gene, directs development of the basal forebrain and visual system [1].
• Finally Emx2 is very interesting from the evolutionary point of view, as it has been shown to share a high degree of homology in its sequence and function with Vax1, another homeobox gene regulating basal forebrain development [9].
• The transcription factor Vax1, an intracellular mediator of both Shh and Fgf signaling, is expressed at high levels in the medial and lateral ganglionic eminences (MGE and LGE, respectively), in the septal area (SA), in the anterior entopeduncular area (AEP) and in the preoptic area (POA) [8].
• These axon guidance defects do not result from the death of normally Vax1(+) midline cells but, instead, correlate with markedly diminished expression of attractive guidance cues in these cells [3].
• Defective postnatal neurogenesis and disorganization of the rostral migratory stream in absence of the Vax1 homeobox gene [7].

References